Ischemic heart disease is a leading cause of mortality due to irreversible damage to cardiac muscle. Inspired by the post-ischemic microenvironment, we devised an extracellular matrix (ECM)–mimicking hydrogel using catalyst-free click chemistry covalent bonding between two elastin-like recombinamers (ELRs). The resulting customized hydrogel included functional domains for cell adhesion and protease cleavage sites, sensitive to cleavage by matrix metalloproteases overexpressed after myocardial infarction (MI). The scaffold permitted stromal cell invasion and endothelial cell sprouting in vitro. The incidence of non-transmural infarcts has increased clinically over the past decade, and there is currently no treatment preventing further functional deterioration in the infarcted areas. Here, we have developed a clinically relevant ovine model of non-transmural infarcts induced by multiple suture ligations. Intramyocardial injections of the degradable ELRs-hydrogel led to complete functional recovery of ejection fraction 21 days after the intervention. We observed less fibrosis and more angiogenesis in the ELRs-hydrogel–treated ischemic core region compared to the untreated animals, as validated by the expression, proteomic, glycomic, and histological analyses. These findings were accompanied by enhanced preservation of GATA4+ cardiomyocytes in the border zone of the infarct. We propose that our customized ECM favors cardiomyocyte preservation in the border zone by modulating the ischemic core and a marked functional recovery. The functional benefits obtained by the timely injection of the ELRs-hydrogel in a clinically relevant MI model support the potential utility of this treatment for further clinical translation.
Background: Cardiac surgery remains the gold standard treatment for select cohorts of patients with coronary artery and valvular heart diseases. It induces an acute systemic inflammatory response due to cardiopulmonary bypass (CPB), myocardial arrest, and surgical trauma. There is growing evidence that increased inflammation leads to greater complications and poorer outcomes for patients post cardiac surgery.Neutrophil/lymphocyte ratio (NLR) is a promising marker of inflammation. This study assessed if NLR could predict postoperative atrial fibrillation and acute kidney injury after cardiac surgery.Methods: A retrospective review of patients undergoing first-time on-pump cardiac surgery was performed.Postoperative atrial fibrillation and acute kidney injury within 7 days of surgery was recorded. Preoperative, day 1, and day 2 NLR were recorded. Potential confounders such as age, sex, comorbidities, and operative factors were included in univariate analysis. Backwards stepwise multivariate regression analysis was performed to identify independent predictors of these complications.Results: Nine hundred and six patients were included for analysis. Higher preoperative NLR was significantly associated with postoperative atrial fibrillation. Day 1 and day 2 NLR were associated with postoperative atrial fibrillation in analyses including all patients. Older age, male gender, preexisting atrial arrhythmias, and higher EuroSCORE II also had a significant association. Diabetes mellitus was protective for postoperative arrhythmias. Preoperative NLR was not significantly associated with acute kidney injury. Day 2 NLR, older age, higher EuroSCORE II, and longer CPB time were independently associated with acute kidney injury post cardiac surgery.Conclusions: Higher preoperative and postoperative NLRs are associated with higher rates of complications post cardiac surgery.
We present a case of a young woman who was initially diagnosed with acute stroke with no obvious risk factors. Preliminary investigation with transthoracic echocardiography and subsequent advanced imaging with transoesophageal echocardiography suggested the diagnosis of a benign cardiac tumour on the anterior leaflet of mitral valve. The patient underwent urgent surgical resection. Histology confirmed the diagnosis of cardiac papillary fibroelastoma. She made complete clinical recovery with no recurrence of symptoms.
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